Background and Motivation
In the near future, biological circuits will be much more
modular and
sophisticated than they are now, with a ten-fold
smaller nucleotide footprint.
The Enabling Technology: Toehold-Mediated Strand Displacement
A
gate strand and
output strand exist as a complex that is
partially bound through complementary Watson-Crick base-pairing within the S2 binding domain. The gate strand also contains an
open, unbound domain called a
toehold region, T*. An input strand with a free complementary toehold region, T, can bind to the toehold region on the gate strand, and subsequently displace the output strand to yield an input-gate complex. This is called a
toehold-mediated strand displacement reaction. The output strand is used as an input for a downstream gate-output complex.
Background
Qian and Winfree (
Science 2011) utilized DNA computation to create AND and OR logic gates
in vitro. They constructed a sophisticated binary square root circuit using these gates:
Each of these:
undergoes the same
toehold-mediated strand displacement reaction. These reactions are fully modular and can be scaled to circuits of any degree of sophistication.
Motivation for Bringing Strand Displacement to Mammalian Synthetic Biology